Brianna Basinger

Introduction. Amyotrophic lateral sclerosis (ALS) is a progressively fatal neurodegenerative disease that causes muscle weakness, atrophy, and death due to respiratory failure.^1,2 Despite the disease’s discovery in 1869, the exact cause of ALS is still unknown and there is no cure.¹ Previous studies have shown that oxidative stress could play a role in the neuronal damage and cell death seen in ALS.^3,4 Edaravone, an FDA approved medication that delays ALS progression, is a free radical scavenger. It is hypothesized that edaravone inhibits neurodegeneration by decreasing oxidative stress, thus, leading to slower neuronal degeneration and death.⁵ Methods. To test if edaravone slows ALS progression, wobbler mice were given either a placebo, low, or high dose of edaravone for 8 weeks. Afterwards, motor neuron density, astrocyte proliferation, and muscle fiber atrophy/strength were measured.⁶ To test if edaravone decreased oxidative stress, one study used two-dimensional gel electrophoresis to analyze proteomic changes in neuroblastoma cells exposed to oxidative stress.⁷ Results. Wobbler mice given the high dose of edaravone showed decreased muscle atrophy and a slower decline in muscle strength. This group of mice also showed an increased number of motor neurons and a lower density of astrocytes.⁶ Furthermore, neuroblastoma cells exposed to oxidative stress were shown to have lower levels of glyceraldehyde 3-phosphatase. Three stress proteins, annexin A1, protein DJ-1, and peroxiredoxin-6, were also found to be upregulated in the cells exposed to oxidative stress. Peroxiredoxin-2 levels, used for managing reactive oxidative species (ROS), were found to be decreased in these cells.⁷ In the neuroblastoma cells expose to oxidative stress and edaravone, the protein levels of glyceraldehyde 3-phosphatase, annexin A1, protein DJ-1, and peroxiredoxin-6 were kept near baseline. Peroxiredoxin-2 levels were found to be elevated in these cells, but they were elevated to a lesser degree compared to cells treated with edaravone alone.⁷ Conclusions. Decreased muscle atrophy, reduced astrocyte density, and increased levels of viable motor neurons indicate that edaravone can slow ALS progression.⁶ Proteomic changes in neuroblastoma cells offer a potential mechanism of action of edaravone. Neuroblastoma cells given edaravone maintained near baseline levels of glyceraldehyde 3-phosphatase, annexin A1, protein DJ-1, and peroxiredoxin- 6; this indicated reduced levels of oxidative stress. Peroxiredoxin-2 levels, indicative of a ROS managing system, were decreased in cells exposed to oxidative stress but increased in cells treated with edaravone.⁷ From these results, edaravone was shown to decrease oxidative stress, reduce neuronal cell death, and, ultimately, delay the progression of ALS.⁵

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